Direct　thrombus　imaging　contributes　to　early　detection　of　thrombosis,　and　animal　models　with　clinical　relevance　are　vital　in　the　development　of　new　thrombolytics.　Here,　a　facile　clot-homing　strategy　is　developed　based　on　the　finding　that　blood　clot　is　negatively　charged.　Positively　charged　pentalysine　moiety　is　coupled　with　phthalocyanine-based　fluorophore,　and　its　applications　in　murine　thromboembolic　models　are　described.　The　probe　efficiently　stains　the　cryosection　of　intracranial　thrombi　retrieved　from　patients　with　cardioembolic　stroke.　In　vitro,　the　fibrin-rich　clot　is　labeled　by　the　probe　at　sub-nanomolar　concentration.　The　probe-labeled　clot　is　formed　into　microparticles　(1–5 µm)　and　intravenously　injected　into　mice　for　pulmonary　embolism　modeling.　In　vivo　imaging　demonstrates　fast　accumulation　and　retention　of　fluorescent　clot　microparticles　in　pulmonary　vessels.　Recombinant　tissue-type　plasminogen　activator　(rtPA)　administration　greatly　reduces　near-infrared　signal　in　the　lungs　in　a　time-dependent　manner.　This　probe　is　also　tested　in　a　stroke　model.　Middle　cerebral　artery　is　occluded　by　autologous　thrombi　formed　under　electric　stimulation.　In　vivo　imaging　shows　that　the　probe　efficiently　homes　to　thrombus　at　early　stage.　Hence,　this　probe　has　great　potential　in　real-time　imaging　of　thromboembolism　in　clinically　relevant　models,　promoting　bench-to-bedside　translation.　This　clot-homing　principle　can　be　used　in　other　applications.　©　2022　Wiley-VCH　GmbH.